The activity of several peptide fragments of parathyroid hormone, alone and in combination with salmon calcitonin and morphine, in antinociceptive tests in the mouse.
Fragments of the parathyroid hormone (PTH) molecule were investigated for intrinsic antinociceptive effects and modulation of salmon calcitonin- and morphine-induced antinociception. Intraventricularly administered PTH 1-34 produced naloxone-insensitive antinociception in both the tail-flick and hot-plate tests. PTH 1-34 antinociceptive effects in the tail-flick test were blocked by i.c.v. salmon calcitonin (sCT, 2 micrograms) and i.c.v. calcium chloride (0.12 mumol). [tyrosine-34]b-PTH (7-34)NH2, the PTH antagonist, did not block PTH 1-34-induced antinociception. PTH 1-34 (2 micrograms) was additive with antinociceptive doses of sCT, but not morphine, in the hot-plate test. PTH 44-68 (0.3 micrograms/mouse, icv.) produced hyperalgesic effects 30 min after administration using the hot-plate test. PTH 44-68 (2 micrograms/mouse) attenuated sCT-induced but not morphine-induced antinociception in both the hot-plate and tail-flick tests. PTH 64-84 was inactive in all tests, alone or in combination with sCT or morphine. Due to the low efficacy of PTH 1-34 and 44-68 in antinociceptive tests, these PTH fragments may act as modulators of antinociception rather than directly producing antinociceptive or hyperalgesic effects. In addition, the results indicate that sCT and the PTH fragments 1-34 and 44-68 may interact in the modulation of nonopiate antinociception, possibly via opposing actions on calcium in the brain.
Welch
S P
SP
Department of Pharmacology & Toxicology, Medical College of Virginia, Richmond.
Dewey
W L
WL
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002116:Calcitonin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006930:Hyperalgesia / Q000139:chemically induced; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*
D000700:Analgesics; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D009020:Morphine; C028815:salmon calcitonin; D002116:Calcitonin; D002118:Calcium